Neurofibromatosis tipo 1 (NF1) y su diagnóstico molecular como estrategia del diagnóstico diferencial y a edades tempranas / Molecular diagnosis as a strategy for differential diagnosis and at early ages of neurofibromatosis type 1 (NF1)

Neurofibromatosis type 1 (NF1), is a haploinsufficient and multisystemic disease, caused by inherited or sporadic mutations in the NF1 gene. Its incidence is one in 2,500 to 3,000 individuals, it has an autosomal dominant pattern of inheritance, high clinical variability, complete penetrance and age-dependent complications. Neurofibromin is the product of the NF1 gene and is believed to act as a tumor suppressor since the loss of its function has been associated with benign and malignant tumors in neural crest-derived tissues. Only two correlations between clinical phenotype and mutant alleles in the NF1 gene have been observed. The established criteria for disease diagnosis are very efficient in adults and children older than 3 years of age, but not for children under this age. Mutational analysis is therefore recommended to confirm the disease in young children with a negative family history. A pathogenic mutation in the NF1 should be added to the list of diagnostic criteria. Mutational analysis is also recommended for differential diagnosis and for prenatal or pre-implantation genetic diagnosis, taking into consideration the family history and the type of method to be applied. Molecular studies of this disease using different complimentary molecular techniques and bioinformatics tools have characterized NF1 gene mutations at both the DNA and mRNA levels, increasing the mutational spectrum. Consequently, about 1,289 defects have been reported to date, mainly nonsense/missense mutations, deletions and splice site defects.

Neurofibromatosis Type I Associated with Malaria: A Case Report and Review of Literature.

Neurofibromatosis (von Recklinghausen disease) is a genetic disorder which is now not been considered to be most common due to a gradual increase in its number of cases worldwide. Its prevalence found is around 1 in 4000-5000 individuals with the incidence been found equally in all regions and reported in almost all ethnic groups. Two-three million cases are reported all over world so far with this disorder. It is an autosomal dominant trait with varied age range of the cases reported from 6 years to late adulthood. Disease occurs by a genetic mutation in the neurofibromatosis Type 1 (NF1) gene (tumor suppressor gene) which is located on chromosome no. 17 at 17q11.2, responsible for coding of neurofibromin, a cytoplasmic protein. The effect of this mutation is elicited in almost all systems of the body with mild to severe complications. About half of the cases reported are present with new mutations in the NF1 genes. A patient afflicted with NF1 has around 50-60% of chances of transmitting the disease to each of his/her offspring. Presenting here a case of the female patient diagnosed malaria associated with NF1.

The Spectrum of NF1 Mutations in Korean Patients with Neurofibromatosis Type 1

Neurofibromatosis type 1 (NF1) is one of the most common autosomal dominant disorders in humans. NF1 is caused by mutations in the NF1 gene which consists of 57 exons and encodes a GTPase activating protein (GAP), neurofibromin. To date, more than 640 different NF1 mutations have been identified and registered in the Human Gene Mutation Database (HGMD). In order to assess the NF1 mutational spectrum in Korean NF1 patients, we screened 23 unrelated Korean NF1 patients for mutations in the coding region and splice sites of the NF1 gene. We have identified 21 distinct NF1 mutations in 22 patients. The mutations included 10 single base substitutions (3 missense and 7 nonsense), 10 splice site mutations, and 1 single base deletion. Eight mutations have been previously identified and thirteen mutations were novel. The mutations are evenly distributed across exon 3 through intron 47 of the NF1 gene and no mutational hot spots were found. This analysis revealed a wide spectrum of NF1 mutations in Korean patients. A genotype- phenotype correlation analysis suggests that there is no clear relationship between specific NF1 mutations and clinical features of the disease.